Impaired renal function in Belgrade rats

VEUTHEY TANIA V; HOFFMANN DANA; VAIDYA VISHAL; WESSLING-RESNICK MARIANNE

Boston

Congreso; Experimental Biology; 2013

Federation of American Societies for Experimental Biology (FASEB)

Belgrade rats carry a disabling mutation in the iron transporter DMT1. Although DMT1 plays a major role in intestinal iron absorption, the transporter is also highly expressed in kidney, where its function remains unknown. Our goal was to characterize renal physiology of Belgrade rats. Animal protocols were approved by the Harvard Medical Area Animal Care and Use Committee. Male Belgrade rats died prematurely with ~50% survival at 20 weeks of age. Necropsy results indicate that renal failure was the major cause of death. By 15 weeks of age, Belgrade rats displayed thickening of glomerular membrane and collagen deposits in tubules and glomeruli. Creatinine clearance was significantly lower compared with heterozygote littermates. Urinary biomarkers of kidney injury, including albumin, fibrinogen and Kim-1, were significantly elevated. Belgrade rat kidney non-heme iron levels were not different from controls but urinary iron excretion was higher. Our results show impaired renal function and altered renal morphology in Belgrade rats, with sclerosis and fibrosis. Loss of DMT1 function results in renal injury, and studies are underway to elucidate the molecular basis.